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NM_000546.6(TP53):c.373_374insACTGTGACTTGCA (p.Thr125fs) AND Li-Fraumeni syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 2, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001056387.6

Allele description [Variation Report for NM_000546.6(TP53):c.373_374insACTGTGACTTGCA (p.Thr125fs)]

NM_000546.6(TP53):c.373_374insACTGTGACTTGCA (p.Thr125fs)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.6(TP53):c.373_374insACTGTGACTTGCA (p.Thr125fs)
HGVS:
  • NC_000017.11:g.7676007_7676008insTTGCAAGTCACAG
  • NG_017013.2:g.16555_16556insACTGTGACTTGCA
  • NM_000546.6:c.373_374insACTGTGACTTGCAMANE SELECT
  • NM_001126112.3:c.373_374insACTGTGACTTGCA
  • NM_001126113.3:c.373_374insACTGTGACTTGCA
  • NM_001126114.3:c.373_374insACTGTGACTTGCA
  • NM_001126118.2:c.256_257insACTGTGACTTGCA
  • NM_001276695.3:c.256_257insACTGTGACTTGCA
  • NM_001276696.3:c.256_257insACTGTGACTTGCA
  • NM_001276760.3:c.256_257insACTGTGACTTGCA
  • NM_001276761.3:c.256_257insACTGTGACTTGCA
  • NP_000537.3:p.Thr125fs
  • NP_001119584.1:p.Thr125fs
  • NP_001119585.1:p.Thr125fs
  • NP_001119586.1:p.Thr125fs
  • NP_001119590.1:p.Thr86fs
  • NP_001263624.1:p.Thr86fs
  • NP_001263625.1:p.Thr86fs
  • NP_001263689.1:p.Thr86fs
  • NP_001263690.1:p.Thr86fs
  • LRG_321t1:c.373_374insACTGTGACTTGCA
  • LRG_321:g.16555_16556insACTGTGACTTGCA
  • NC_000017.10:g.7579313_7579314insTGCAAGTCACAGT
  • NC_000017.10:g.7579325_7579326insTTGCAAGTCACAG
  • NM_000546.5:c.373_374insACTGTGACTTGCA
Protein change:
T125fs
Links:
dbSNP: rs2073448940
NCBI 1000 Genomes Browser:
rs2073448940
Molecular consequence:
  • NM_000546.6:c.373_374insACTGTGACTTGCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001126112.3:c.373_374insACTGTGACTTGCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001126113.3:c.373_374insACTGTGACTTGCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001126114.3:c.373_374insACTGTGACTTGCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001126118.2:c.256_257insACTGTGACTTGCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001276695.3:c.256_257insACTGTGACTTGCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001276696.3:c.256_257insACTGTGACTTGCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001276760.3:c.256_257insACTGTGACTTGCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001276761.3:c.256_257insACTGTGACTTGCA - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Li-Fraumeni syndrome (LFS)
Synonyms:
Sarcoma family syndrome of Li and Fraumeni
Identifiers:
MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001220828Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 2, 2019) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes.

Ruijs MW, Verhoef S, Rookus MA, Pruntel R, van der Hout AH, Hogervorst FB, Kluijt I, Sijmons RH, Aalfs CM, Wagner A, Ausems MG, Hoogerbrugge N, van Asperen CJ, Gomez Garcia EB, Meijers-Heijboer H, Ten Kate LP, Menko FH, van 't Veer LJ.

J Med Genet. 2010 Jun;47(6):421-8. doi: 10.1136/jmg.2009.073429.

PubMed [citation]
PMID:
20522432

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001220828.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with TP53-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr125Asnfs*28) in the TP53 gene. It is expected to result in an absent or disrupted protein product.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024